Sticks and Stones May Break Your Bones, But Sophie Morgani Will Fix Them With Stem Cells

In NYSCF – Druckenmiller Postdoctoral Fellow Sophie Morgani’s lab, run by Philipp Leucht at the NYU Grossman School of Medicine, there’s a bit of a curse. The team studies bones, and as soon as someone new joins, they tend to break one.

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“I haven’t broken a bone yet, but there seems to be a jinx that once you come in [the lab], that’s the time,” she laughs. “I’m one year in, and luckily I’m still fine! At least if I did break one, I’d be surrounded by bone experts.” 

Fingers crossed that Sophie doesn’t succumb to the bone-breaking curse – she’s got much more important things to focus on: for example, learning how to preserve and repair bones with stem cells.

What brought her to study this increasingly important topic, what advice would she give young scientists, and what’s next for her research? Read on to find out.

What made you decide to become a scientist?

Since I was a child, I’ve loved learning, and I had amazing science teachers. Although there are so many career options in science, like being a medical doctor, I was most excited by the idea of being at the forefront of what’s unknown and discovering new things. 

Then as I got older, I became more interested in contributing something positive to society, and I’m happy that I get to do that as a scientist as well.

What made you interested in stem cells?

I did my undergraduate degree in biochemistry, not in stem cells, and it was something that was quite different. By the time I finished that, I realized that wasn’t for me [laughs].

Stem cells were just starting to become a bigger area for research (Shinya Yamanaka had just won the Nobel Prize for his findings in induced pluripotent stem cells), and I was really excited by their therapeutic potential for drug testing or cell replacement therapies. It was – and is – such a rapidly developing field. 

What made you interested specifically in bone health?

Our population is rapidly aging, and bone health is such a pressing issue that we have to deal with. Although people rarely die from having a broken bone, it’s often the first event that can lead to a downward spiral of health. 

Bone is really cool as well because it’s one of the few tissues in a human that can fully regenerate. So normally if we get an injury in other tissues, it will heal, but you get a scar, whereas bone just fully regenerates as if it was never broken. I think understanding how and why it can do this is really interesting, and can hopefully inform how we think about regenerating different tissues.

I really only came into the bone field about a year ago, and I was guilty of just thinking of it as a passive structure – like a scaffold for our body – but it does much more important things than that. You make all of your blood cells in your bone, and it regulates metabolism and stores minerals. There’s so much that it does.

How do our bones change as we age?

As we get older, we produce less bone, and our bone is broken down more. And also the inside of our bones, which is normally full of the stem cells that make your blood, turns to fat. Together, this change in the structure makes these bones much more fragile and more likely to break. So a lot of the therapies at the moment focus on reducing the breakdown of the bone as we get older, but there are less that are able to boost the process of making new bone. 

Another challenge is working with the stem cells. I’ve realized there are still a lot of open questions to do with the stem cells in bone compared to other organs. In many organs, stem cells can be found in a very defined location: we know exactly where they are and how to identify them, but in bone, it seems like there are maybe many different kinds of stem cells and they’re spread throughout different locations. So just identifying them is still a bit of a challenge. 

Also bone can be a challenging tissue to work with because it’s this hard, calcified structure on the outside and this soft center. When we would normally cut sections of tissues to look at them under a microscope, bone will just kind of crumble apart. So just being able to visualize the tissue is a challenge. There are a lot of things to work on. 

How does your lab use stem cells to research bone disease?

What we do is extract the stem cells from bone and grow them in a dish. We can then push them to make all of the cell types that they normally would in our bones, which are the bone-producing cells called osteoblasts as well as fat and cartilage. And then we investigate how different genetic mutations that might be leading to diseases or aging, or different drugs, affect the function of those stem cells. We also look inside mice to see how those different factors affect the function of their bone cells. And we try to identify the specific molecular factors that cause these changes in stem cell function and how we might be able to then manipulate them.

How do you hope that this will one day have an impact for patients?

One of the big questions our lab studies is how aging affects skeletal stem cells. So, as I was saying, you produce less bone as you age, and our lab has shown that this is due to a loss in the number of functional skeletal stem cells. So, we’re looking at the very basic mechanisms of how that happens – what changes in these stem cells – with the big aim of discovering new targets and drugs that may be able to reverse these changes and either maintain the health of the skeleton in elderly individuals, or even rejuvenate bones. 

What do you hope to achieve in your career in research?

Of course we all want to have that massive scientific breakthrough that’s Nobel Prize-worthy, but someone once told me something that really stuck. And that was that there are very few Nobel Prize winners, and our biggest contribution to science is probably not going to be our scientific research, but our training of younger people in the field and passing on that knowledge. So I feel quite strongly about that as well. One person can have such a huge impact through the people that they train. And hopefully from passing on our experience they will be even better than we are. 

What advice would you give to a young person who’s interested in pursuing STEM?

The advice I wish I’d had is to really look at what options you have in STEM, because I don’t think I had access to the information I needed when I was younger. There are so many different career options: you could be a researcher, a communicator, a doctor, a policymaker.  So just to try and educate yourself on the different possibilities, because there are so many that aren’t obvious. 

And it’s really great if you can get hands-on experience through internships. So for my undergraduate degree, I did biochemistry, and as part of that degree, I opted to have a year working in a biochemistry lab. And that was a point when I realized I didn’t particularly like it [laughs]. And that’s valuable information! The more experience you can get, you can see what you like and what you don’t, and it’s always possible to adjust course.

How have you seen the importance of diversity, equity, inclusion, and belonging (DEIB) in STEM throughout your career?

I’m definitely aware of the lack of diversity in STEM. And I know that that’s not due to a lack of interest in the field from people of different communities and backgrounds, but rather a lack of access to information and opportunities.

I am the first person in my family to go to university at all, and I sort of stumbled into this by chance. So I want to try and give other people access to the information that I didn’t have. I am part of a mentorship program at NYU called Clear Direction Mentoring where we take in students at critical transitions in their career, for example, between high school and college. We give them experience in STEM and just talk through questions that they have about their career and try to help them make those decisions. So I think it’s really important [to foster DEIB in STEM] and I think we as scientists have a responsibility to try and improve that situation where we can. Having people in research with different life experiences and therefore different ways of thinking is essential for the scientific process. 

What is most exciting to you about receiving this award and joining the NYSCF Innovator community?

For me it really is the community, and I’ve experienced it a lot already. When NYSCF announced the awardees for the fellowships, I very quickly got emails from other people with the fellowship to say congratulations and looking forward to seeing you at the conferences. I can see it will be a really supportive community to be part of. 

I also think that being in our specific fields, we get stuck going to certain conferences and interacting with the same people that do very similar research. So, going to the NYSCF retreats and so on, and being able to interact with people working in different fields is going to be a new opportunity and hopefully could lead to really interesting collaborations.